Human apyrase represents a highly promising therapy to prevent or reduce ischemia-reperfusion injury during lung transplantation. The enzyme strongly preserves vascular integrity and inhibits platelet activation and aggregation without increasing bleeding risk. Using a protein informatics approach, we have successfully engineered an optimized human apyrase, APT102. With Phase II grant support, We will determine whether APT102 improves lung allograft function without increasing bleeding risk in clinically relevant models of allogeneic orthotopic lung transplantation in rats and dogs. The ultimate goal is to demonstrate whether APT102 has the potential to be a therapy for transplantation-associated and other vascular diseases. PUBLIC HEALTH RELEVANCE: We will determine whether human apyrase improves lung allograft function without increasing bleeding risk in clinically relevant models of allogeneic orthotopic lung transplantation in rats and dogs.